Anti‐viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia‐recombinant virus expressing LCMV‐WE nucleoprotein or glycoprotein

Abstract

The viral antigen specificity of primary cytotoxic T cell responses (CTL) of H-2b, H-2k, H-2q, H-2s, H-2f and some H-2-recombinant mice against lymphocytic choriomeningitis virus (LCMV-WE isolate) as well as the specificity of some CTL clones and T cell lines was defined on target cells infected with vaccinia-recombinant virus expressing nucleoprotein (Np) or glycoprotein (Gp). Np was recognized together with H-2q (Dq), H-2d (DLd), H-2s and H-2b (Db). Gp specificity was restricted to H-2f and H-2b (Kb and Db); H-2k-restricted CTL anti-LCMV responses were neither Gp nor Np specific. The anti-viral protective immunity induced by vaccinia-Gp or vaccinia-Np recombinants was evaluated in mice. In vivo protection was T cell mediated by class I restricted Ly-2+ T cells; it correlated well with the CTL specificity defined in vitro. Some of the CTL-nonresponder H-2 allele plus Np or H-2 plus Gp combinations were, however, protected to variable and low degrees by vaccinia-recombinant viruses, indicating that anti-viral protection is a more sensitive readout for CTL activity than the in vitro assay. For example, B10.D2 H-2d mice generated measurable CTL responses only to Np; after immunization with a vaccinia-Np recombinant, LCMV titers were 10(4) times lower in spleens than in vaccinia-primed controls. Although vaccinia-Gp-immunized BALB/c mice revealed no CTL activity in vitro, they nevertheless had 10(2) times lower LCMV titers in spleens than controls. Anti-viral protection, particularly in low-responder combinations, was usually short-lived and diminished after 3 weeks. In a high-responder situation, protection was of a longer duration (greater than 8 weeks). Vaccination with vaccinia-Np or Gp recombinants protected mice against lethal T cell-mediated lymphocytic choriomeningitis induced by LCMV or prevented the local footpad swelling reaction; these in vivo effects were H-2 dependent and followed the identical roles established for CTL recognition in vitro.

Efficacy of individual measles virus structural proteins in the protection of rats from measles encephalitis

“…Although for most viruses the components responsible for the induction of protective immunity have been shown to be membrane-bound glycoproteins, clinical protection from systemic viral disease following vaccination with VV recombinants expressing internal and even non-structural proteins has been described for a number of other viruses such as Lassa fever virus and influenza virus in different animal species (Hany et al, 1989;Mackett, 1990;Putnak & Schlesinger, 1990). However, comparative analyses of the efficacy of different individual virus proteins in the induction of antiviral immunity are rare (Andrews & Coupar, 1988).…”

Cutting Edge: Competition for APC by CTLs of Different Specificities Is Not Functionally Important During Induction of Antiviral Responses

“…rVV encoding the LCMV glycoprotein (VV-G2) was obtained from Dr. D. Bishop (Institute of Virology, Oxford, U.K.) and was propagated on BSC40 cells (24).…”

Cytotoxic T Lymphocyte Control of Acute Lymphocytic Choriomeningitis Virus Infection: Interferon , but Not Tumour Necrosis Factor , Displays Antiviral Activity in vivo

“…DISCUSSION In animal models, CTL have been shown to play an important role in the control of several viral infections, including those caused by influenza virus, LCMV, murine cytomegalovirus and respiratory syncytial virus (Lin & Askonas, 1981 ;Lukacher et al, 1984;Reddehase et al, 1987;Cannon et al, 1987;Moskophidis et aL, 1987). However, because of the restricting role played by major histocompatibility glycoproteins in selecting unique and varied portions of different viral proteins (Ahmed et al, 1984;Whitton et al, 1988Whitton et al, , 1989Hany et al, 1989;Bennink et al, 1987) for CTL recognition and lysis of virus-infected targets, the therapeutic use of CTL in an outbred population like man presents difficulties. For that reason, the earlier observation that a presumed soluble factor from CTL (Oldstone et al, 1986;Ahmed et al, 1987) effectively cleared viral materials deposited in cells in vivo is of interest.…”